A Study of IMC-A12 in Participants With Tumors Who No Longer Respond to Treatment or For Whom No Treatment is Available
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00785538
Collaborator
(none)
24
3
1
63
8
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if IMC-A12 is safe for participants, and also to determine the best dose of IMC-A12 to give to participants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
The purpose of this study is to establish the safety profile and maximum tolerated dose (MTD) of the anti-IGF-IR monoclonal antibody IMC-A12 administered weekly in participants with advanced solid tumors who no longer respond to standard therapy or for whom no standard therapy is available
Study Design
Study Type:
Interventional
Actual Enrollment
:
24 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I Study of Anti-Insulin-Like Growth Factor-I Receptor (IGF-IR) Monoclonal Antibody IMC-A12 in Patients With Advanced Solid Tumors Who No Longer Respond to Standard Therapy or for Whom No Standard Therapy is Available
Study Start Date
:
Oct 1, 2005
Actual Primary Completion Date
:
Jan 1, 2011
Actual Study Completion Date
:
Jan 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMC-A12 All participants will receive intravenous (I.V.) infusions of IMC-A12, with the dose depending on which cohort they are enrolled into. A minimum of three participants will be enrolled in each cohort. When all participants complete a cohort, dose escalation to the next cohort will occur. |
Biological: IMC-A12
Cohort 1
3 milligrams/kilogram (mg/kg), I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
Biological: IMC-A12
Cohort 2
6 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
Biological: IMC-A12
Cohort 3
10 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
Biological: IMC-A12
Cohort 4
15 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
Biological: IMC-A12
Cohort 5
21 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
Biological: IMC-A12
Cohort 6
27 mg/kg, I.V. once a week, for 4 weeks, followed by a 2-week observation period.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) or Deaths [Enrollment to study completion up to 215 weeks]
Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module.
- Maximum Tolerated Dose (MTD) [6 weeks]
The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12.
Secondary Outcome Measures
- Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
- Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
- Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
- Half-Life (t1/2) of IMC-A12 Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
Half-Life (t1/2) is the time measured for the plasma concentration of the drug to decrease by one half. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
- Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.
- Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses [Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1]
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data.
- Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity) [Before the last infusion of each treatment cycle]
Analysis was not performed due to lack of available assay.
- Number of Participants With Best Overall Response [Enrollment to study completion up to 215 weeks]
Stable Disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD). PR and PD were assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants with a global deterioration of their health status requiring discontinuation of treatment without objective evidence of disease progression at that time were to be reported as "symptomatic deterioration"
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histopathologically-documented, measurable, advanced primary or recurrent solid tumors that no longer respond to standard therapy or for which no standard therapy is available.
-
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2 at study entry
-
Able to provide written informed consent
-
Life expectancy of >3 months
-
Adequate hematologic functions, as defined by: absolute neutrophil count (ANC) ≥1500/cubic millimeter (mm³), hemoglobin level ≥10 grams/deciliter (gm/dL), platelet count ≥100,000/mm³
-
Adequate hepatic function, as defined by: total bilirubin level ≤1.5 x the upper limit of normal (ULN), aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤2.5 x the ULN or ≤5 x the ULN if known liver metastases
-
Adequate renal function, as defined by a serum creatinine level ≤1.5 x the ULN
-
Ejection fraction within the normal institutional limits
-
Use of effective contraception per institutional standard, if procreative potential exists
-
At least 28 days must have elapsed from major surgery, prior chemotherapy, prior treatment with an investigational agent or device, prior radiation therapy (palliative radiation therapy is allowed), an open biopsy, or a significant traumatic injury to allow for adequate recovery. Ongoing side effects due to these agents must be ≤Grade 2 prior to entering the study.
-
At least 6 weeks must have elapsed from nitrosoureas, mitomycin C, or monoclonal antibody [not targeting the insulin-like growth factor receptor (IGFR)] therapy to allow for adequate recovery. Ongoing side effects due to these agents must be ≤Grade 2 prior to entering the study.
-
Accessible for treatment and follow-up. Participants enrolled in this trial must be treated at the participating center.
Exclusion Criteria:
-
Any concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix. Participants with a previous malignancy but without evidence of disease for ≥3 years will be allowed to enter the trial.
-
Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, angioplasty, stenting or myocardial infarction within 6 months, uncontrolled hypertension, clinically significant cardiac arrhythmia, psychiatric illness/social situations that would compromise participant safety or limit compliance with study requirements, participants with symptomatic brain metastases
-
Serious or nonhealing active wound, ulcer or bone fracture
-
Know human immunodeficiency virus (HIV)-positive
-
History of hemorrhagic or thrombotic disorder within 9 months
-
Proteinuria ≥1+ by routine urinalysis (participants with a protein value of ≤500 milligrams (mg) confirmed by a 24-hour urine collection are eligible)
-
Pregnant [confirmed by serum beta human chorionic gonadotropin (βHCG)] or breast feeding
-
History of prior treatment with other agents specifically targeting IGFRs
-
Known diabetes
-
Inability or unwillingness to interrupt steroidal or hormonal therapy for the duration of treatment with IMC-A12
-
Positive anti-IMC-A12 antibody response
-
History of allergic reactions to monoclonal antibodies or other therapeutic proteins
-
Employees of the investigator or study center with direct involvement in this study or other studies under the direction of the investigator or study center, as well as family members of the employees.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ImClone Investigational Site | Scottsdale | Arizona | United States | 85258 |
| 2 | ImClone Investigational Site | Detroit | Michigan | United States | 48201 |
| 3 | ImClone Investigational Site | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00785538
Other Study ID Numbers:
- 13932
- CP13-0501
- I5A-IE-JAEH
First Posted:
Nov 5, 2008
Last Update Posted:
Jan 8, 2019
Last Verified:
Dec 1, 2018
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | For participants enrolled under Protocol Versions 1.0 and 2.0, there was a 2-week pharmacokinetic (PK) period prior to Cycle 1. |
|---|---|
| Pre-assignment Detail | After completion of the 10 milligrams/kilogram (mg/kg) cohort, PK data were obtained that established a recommended dose for Phase 2 studies. Enrollment and dose escalation beyond 15 mg/kg was stopped. Participants with progressive disease (PD) or death were considered to have completed the study. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered intravenously (I.V.) on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with stable disease (SD) could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Period Title: PK Period | ||||
| STARTED | 7 | 1 | 1 | 0 |
| COMPLETED | 7 | 1 | 1 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: PK Period | ||||
| STARTED | 7 | 9 | 6 | 2 |
| Received at Least 1 Dose of Study Drug | 7 | 9 | 6 | 2 |
| COMPLETED | 6 | 7 | 4 | 1 |
| NOT COMPLETED | 1 | 2 | 2 | 1 |
Baseline Characteristics
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | Total of all reporting groups |
| Overall Participants | 7 | 9 | 6 | 2 | 24 |
| Age (years) [Median (Full Range) ] | |||||
| Median (Full Range) [years] |
65.7
(10.43)
|
56.4
(6.30)
|
59.4
(15.17)
|
42.9
(15.13)
|
57.2
(11.13)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
42.9%
|
5
55.6%
|
1
16.7%
|
1
50%
|
10
41.7%
|
| Male |
4
57.1%
|
4
44.4%
|
5
83.3%
|
1
50%
|
14
58.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
4
57.1%
|
8
88.9%
|
5
83.3%
|
1
50%
|
18
75%
|
| Black |
1
14.3%
|
1
11.1%
|
0
0%
|
1
50%
|
3
12.5%
|
| Asian |
1
14.3%
|
0
0%
|
1
16.7%
|
0
0%
|
2
8.3%
|
| Hispanic |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
1
4.2%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
7
100%
|
9
100%
|
6
100%
|
2
100%
|
24
100%
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) or Deaths |
|---|---|
| Description | Data presented are the number of participants who experienced serious adverse events (SAEs), other non-serious AEs and deaths during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Event module. |
| Time Frame | Enrollment to study completion up to 215 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 7 | 9 | 6 | 2 |
| SAEs |
2
28.6%
|
3
33.3%
|
2
33.3%
|
0
0%
|
| AEs |
7
100%
|
8
88.9%
|
6
100%
|
2
100%
|
| Death due to PD |
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Title | Maximum Tolerated Dose (MTD) |
|---|---|
| Description | The MTD was defined as the dose preceding the dose level at which 2 participants experienced a dose-limiting toxicity (DLT). A DLT was defined as any Grade 3 or 4 hematologic or nonhematologic toxicity based on Common Terminology Criteria for AE (CTCAE), excluding alopecia, which was considered by the investigator to be definitely, probably, or possibly related to IMC-A12. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug and completed Cycle 1 and 2-week observation or discontinued treatment for an IMC-A12-related toxicity. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 6 | 7 | 5 | 1 |
| Number [mg/kg] |
NA
|
NA
|
NA
|
NA
|
| Title | Maximum Concentration (Cmax) of IMC-A12 Following Multiple Doses |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate Cmax. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 4 | 3 | 1 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms/milliliter (µg/mL)] |
292
(42)
|
385
(51)
|
734
(NA)
|
965
(NA)
|
| Title | Observed Serum Concentration of IMC-A12 at 168 Hour Post End of Infusion Following Multiple Doses |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate Cmin. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 3 | 2 | 1 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [µg/mL] |
74.8
(28)
|
154
(NA)
|
226
(NA)
|
122
(NA)
|
| Title | Area Under the Serum Concentration Versus Time Curve of IMC-A12 During One Dosing Interval (AUCτ) Following Multiple Doses |
|---|---|
| Description | |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate AUCτ. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 3 | 2 | 1 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [micrograms*hour/milliliter (µg*h/mL] |
19800
(39)
|
36350
(NA)
|
66700
(NA)
|
49300
(NA)
|
| Title | Half-Life (t1/2) of IMC-A12 Following Multiple Doses |
|---|---|
| Description | Half-Life (t1/2) is the time measured for the plasma concentration of the drug to decrease by one half. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data. |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate t1/2. Zero participants were analyzed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 2 | 0 | 0 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [days] |
6.19
(NA)
|
6.17
(NA)
|
| Title | Clearance Rate of IMC-A12 at Steady State (CLss) Following Multiple Doses |
|---|---|
| Description | CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state. |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate CLss. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 3 | 2 | 1 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters/hour (L/h)] |
0.0124
(40)
|
0.0125
(NA)
|
0.0114
(NA)
|
0.0296
(NA)
|
| Title | Volume of Distribution of IMC-A12 at Steady State (Vss) Following Multiple Doses |
|---|---|
| Description | Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug at steady-state. The analysis was not performed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data. |
| Time Frame | Predose, 0.5, 1, 2, 4, 8, 24, 48, 96, 168, 264 and 336 hours after the infusion of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received study drug and had PK data available to calculate Vss. Zero participants were analyzed for the 6 mg/kg and 10 mg/kg dosing groups due to insufficient PK data. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 2 | 0 | 0 | 1 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters (L)] |
2.88
(NA)
|
5.19
(NA)
|
| Title | Serum Anti-IMC-A12 Antibody Assessment (Immunogenicity) |
|---|---|
| Description | Analysis was not performed due to lack of available assay. |
| Time Frame | Before the last infusion of each treatment cycle |
Outcome Measure Data
| Analysis Population Description |
|---|
| Zero participants were analyzed due to lack of available assay. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Number of Participants With Best Overall Response |
|---|---|
| Description | Stable Disease (SD) is neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD). PR and PD were assessed by investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PR is ≥30% decrease in sum of longest diameter of target lesions. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. Participants with a global deterioration of their health status requiring discontinuation of treatment without objective evidence of disease progression at that time were to be reported as "symptomatic deterioration" |
| Time Frame | Enrollment to study completion up to 215 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants. |
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. |
| Measure Participants | 7 | 9 | 6 | 2 |
| Stable Disease (SD) |
2
28.6%
|
1
11.1%
|
2
33.3%
|
1
50%
|
| Progressive Disease (PD) |
5
71.4%
|
4
44.4%
|
2
33.3%
|
1
50%
|
| Symptomatic Deterioration |
0
0%
|
3
33.3%
|
0
0%
|
0
0%
|
| Not Evaluable |
0
0%
|
1
11.1%
|
2
33.3%
|
0
0%
|
| Partial Response (PR) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg | ||||
| Arm/Group Description | 3 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 3 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 6 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 6 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 10 mg/kg IMC-A12 administered I.V. on Day 1 of a 2-week PK period prior to Cycle 1. 10 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | 15 mg/kg IMC-A12 administered I.V. once a week for 4 weeks, for a total of 4 doses per cycle. Cycle 1 was followed by a 2-week observation. Participants with an objective response after Cycle 1 could have received additional treatment cycles at the same dose and schedule until disease progression or withdrawal criteria were met. Participants with SD could have received up to 2 additional 4-week treatment cycles at the same dose and schedule. | ||||
All Cause Mortality |
||||||||
| 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/7 (28.6%) | 3/9 (33.3%) | 2/6 (33.3%) | 0/2 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| DIARRHOEA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| DUODENAL ULCER HAEMORRHAGE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| NAUSEA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| VOMITING | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| General disorders | ||||||||
| ASTHENIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| DISEASE PROGRESSION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| NON-CARDIAC CHEST PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Infections and infestations | ||||||||
| BACTERAEMIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| PNEUMONIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| DEHYDRATION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| CANCER PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| PELVIC PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| COUGH | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| DYSPNOEA | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| HAEMOPTYSIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| PNEUMONIA ASPIRATION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| PULMONARY EMBOLISM | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| 3 mg/kg | 6 mg/kg | 10 mg/kg | 15 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 8/9 (88.9%) | 6/6 (100%) | 2/2 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/2 (50%) | 1 |
| IRON DEFICIENCY ANAEMIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| NEUTROPENIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Cardiac disorders | ||||||||
| BRADYCARDIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| DIASTOLIC DYSFUNCTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| TACHYCARDIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Eye disorders | ||||||||
| VISUAL DISTURBANCE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| ABDOMINAL PAIN | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| ASCITES | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| CONSTIPATION | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 2/6 (33.3%) | 2 | 1/2 (50%) | 1 |
| DIARRHOEA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| DYSPEPSIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| FAECES DISCOLOURED | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| FOOD POISONING | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| GINGIVAL PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 2 |
| NAUSEA | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 2/6 (33.3%) | 2 | 2/2 (100%) | 3 |
| ORAL PAIN | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| RECTAL PROLAPSE | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| TOOTHACHE | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| VOMITING | 2/7 (28.6%) | 2 | 2/9 (22.2%) | 2 | 2/6 (33.3%) | 2 | 1/2 (50%) | 1 |
| General disorders | ||||||||
| ASTHENIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| CHEST DISCOMFORT | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| CHILLS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| EARLY SATIETY | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| FATIGUE | 2/7 (28.6%) | 2 | 2/9 (22.2%) | 3 | 5/6 (83.3%) | 5 | 1/2 (50%) | 2 |
| GAIT DISTURBANCE | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| INFUSION RELATED REACTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| NODULE | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| NON-CARDIAC CHEST PAIN | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| OEDEMA PERIPHERAL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 2 | 1/2 (50%) | 1 |
| Hepatobiliary disorders | ||||||||
| HEPATIC PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Infections and infestations | ||||||||
| FUNGAL INFECTION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| GASTROENTERITIS VIRAL | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| HELICOBACTER INFECTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| INFLUENZA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| RESPIRATORY TRACT INFECTION VIRAL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| UPPER RESPIRATORY TRACT INFECTION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| URINARY TRACT INFECTION | 1/7 (14.3%) | 3 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| VIRAL INFECTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| INCISION SITE COMPLICATION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| THERMAL BURN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Investigations | ||||||||
| DENTAL EXAMINATION ABNORMAL | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| SPUTUM ABNORMAL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| WEIGHT DECREASED | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| WEIGHT INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| ANOREXIA | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 1/6 (16.7%) | 1 | 1/2 (50%) | 1 |
| DECREASED APPETITE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| DEHYDRATION | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| HYPERGLYCAEMIA | 2/7 (28.6%) | 2 | 0/9 (0%) | 0 | 2/6 (33.3%) | 3 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| ARTHRALGIA | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 0/6 (0%) | 0 | 1/2 (50%) | 2 |
| BACK PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| BONE PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| CHEST WALL PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 1/2 (50%) | 1 |
| COSTOCHONDRITIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| FLANK PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| MUSCLE SPASMS | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| MYALGIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| OSTEONECROSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| OSTEOPENIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| PAIN IN EXTREMITY | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| SHOULDER PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 1/2 (50%) | 2 |
| Nervous system disorders | ||||||||
| DIZZINESS | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 2 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| HEADACHE | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| SENSORY DISTURBANCE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Psychiatric disorders | ||||||||
| INSOMNIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| MICTURITION URGENCY | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| NEPHROPATHY TOXIC | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| URINARY INCONTINENCE | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||
| PELVIC PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| TESTICULAR PAIN | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 1/1 (100%) | 1 |
| VAGINAL DISCHARGE | 0/3 (0%) | 0 | 0/5 (0%) | 0 | 1/1 (100%) | 1 | 0/1 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| BREATH SOUNDS DECREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| COUGH | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| CRACKLES LUNG | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| DYSPNOEA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| DYSPNOEA EXERTIONAL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| EPISTAXIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| HAEMOPTYSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| NASAL CONGESTION | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| PHARYNGOLARYNGEAL PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| POSTNASAL DRIP | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| RHINORRHOEA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| WHEEZING | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| ACNE | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| DRY SKIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| PRURITUS | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| PSORIASIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| RASH | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| URTICARIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Vascular disorders | ||||||||
| VARICOSE VEIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00785538
Other Study ID Numbers:
- 13932
- CP13-0501
- I5A-IE-JAEH
First Posted:
Nov 5, 2008
Last Update Posted:
Jan 8, 2019
Last Verified:
Dec 1, 2018